Appetitively Motivated Instrumental Learning in SynGAP Heterozygous Knockout Mice

Mary Muhia, Joram Feldon, Irene Knuesel, Kay Yan Benjamin Yee

Research output: Journal article publicationJournal articleAcademic researchpeer-review

12 Citations (Scopus)


The synaptic Ras/Rap-GTPase-activating protein (SynGAP) regulates specific intracellular events following N-methyl-d-aspartate receptor (NMDAR) activation. Here, the impact of SynGAP heterozygous knockout (SG +/-) on NMDAR-dependent functions was assessed using different positive reinforcement schedules in instrumental conditioning. The knockout did not affect the temporal control of operant responding under a fixed interval (FI) schedule, but led to a putative enhancement in response vigor and/or disinhibition. When examined on differential reinforcement of low rates of response (DRL) schedules, SG +/- mice showed increased responding under DRL-4s and DRL-8s, without impairing the response efficiency (total rewards/total lever presses) because both rewarded and nonrewarded presses were elevated. Motivation was unaffected as evaluated using a progressive ratio (PR) schedule. Yet, SG +/- mice persisted in responding during extinction at the end of PR training, although an equivalent phenotype was not evident in extinction learning following FI-20s training. This extinction phenotype is therefore schedule-specific and cannot be generalized to Pavlovian conditioning. In conclusion, constitutive SynGAP reduction increases vigor in the execution of learned operant behavior without compromising its temporal control, yielding effects readily distinguishable from NMDAR blockade.
Original languageEnglish
Pages (from-to)1114-1128
Number of pages15
JournalBehavioral Neuroscience
Issue number5
Publication statusPublished - 1 Oct 2009
Externally publishedYes


  • conditioned freezing
  • NMDA receptor
  • operant conditioning
  • response inhibition
  • temporal discrimination

ASJC Scopus subject areas

  • Behavioral Neuroscience


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